Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies (32,000 deaths per year). Because of its aggressive growth and rapid metastasis to lymph nodes and liver, only 10% to 15% of patients are found to be resectable at diagnosis (1). Currently, the most common strategy for the treatment of advanced pancreatic cancer is treatment with gemcitabine, although the median survival time continues to be <6 months for these patients (2, 3). Recently, several types of inhibitors targeting the epidermal growth factor (EGF) receptor, platelet-derived growth factor (PDGF) receptor, and nuclear factor-nB (NF-nB) have shown their effectiveness in pancreatic cancer in murine models (4-7). In clinical trials, EGF receptor tyrosine kinase inhibitor (Erlotinib, Tarceva) plus gemcitabine enhances 1-year survival for patients with advanced pancreatic cancer (8). However, the difference in median survival between Erlotinib plus gemcitabine group and gemcitabine alone group is <1 month. An effective new approach is needed for management of patients with this disease.
Gemcitabine (Gemzar) is a widely accepted first-line therapy for advanced pancreatic cancer, although the median survival time continues to be <6 months for these patients (2, 3). As most studies using single agent show low response rate and little effect on patient survival in advanced adenocarcinoma, several clinical trials using a combined approach of radiotherapy and/or molecular target therapy with gemcitabine have been initiated (33). In vitro studies have reported synergistic effect of gemcitabine with cisplatin, fluvastatin hydroxymethylglutaryl-CoA reductase inhibitor, CpG-oligodeoxynucleotides, EGFR, PDGF, and vascular endothelial growth factor inhibitor targeting drugs (6, 34-37). In addition, immunotoxins were shown to exert synergistic effect with chemotherapeutic drugs, for example, doxorubicin plus anti-B4-blocked ricin, Ara-C plus granulocyte macrophage colony-stimulating factor fused to truncated diphtheria toxin (DT388-GM-CSF), and fludarabine with rituximab saporin-S6 conjugated protein (38-40).